It is known that resin-modified glass-ionomer cement (RMGIC) is an attractive dental restorative because it has enhanced mechanical strength, bonding and handling properties. However, a disadvantage of this cement is that it contains a large quantity of 2-hydroxyethyl methacrylate (HEMA). Since unreacted HEMA is cytotoxic to pulp and surrounding tissues, elimination of HEMA could make this "intelligent" cement more attractive for both dental and orthopedic applications. We have demonstrated that new and novel amino acid-modified and non-HEMA containing RMGICs exhibit significantly improved mechanical strengths, adhesion and self-etching capabilities. The objective of this research is to develop these novel amino acid based glass-ionomers for both dental and orthopedic applications, in response to NIBIB's RFA for development of novel biomaterials with improved biological and mechanical properties. In this research, inexpensive and biostable amino acid-based polycarboxylic acid will be synthesized and formulated with amino acid derivatives to form an innovative non-HEMA containing RMGIC system. Design of Experiment (DOE) methodology will be applied to optimize molar ratio, molecular weight, grafting ratio of synthesized poly(amino acid), formulations and filler contents. Mechanical strengths and other physical properties of the new cements will be evaluated. The proposed amino acid-based cements will provide extra salt-bridges, thus enhancing adhesion and mechanical strengths. In vitro direct cell contact as well as methylthiazolyldiphenyl tetrazolium (MTT) studies and in vivo bone response will be conducted to determine the biocompatibility and bioactivity of the new cements. Novel restoratives for both dentistry and orthopedics should be an outcome of this basic research to establish commercial biomaterials for future industrial development. Successful achievement of the goal of this project will significantly impact the field of restorative dentistry and orthopedic surgery. This project will create a university-wide collaboration between synthetic polymer chemist, biomaterials scientist, biomechanical engineer and clinical dentist. This project will also provide an ideal training environment for biomedical engineering students because it will allow them, through close interactions with the collaborators from different disciplines, to develop a broad perspective on biomaterials research.